Nef Binds and activates the Src-family tyrosine kinase Fyn

Stable Identifier
R-HSA-200908
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Nef has been shown to bind specifically to a subset of the Src family of kinases. Nef/Fyn interaction centers on a proline-rich motif (Pro-x-x-Pro), which is implicated in SH3 binding. This domain is partially disordered in the absence of the binding partner; when bound this motif fully adopts a left-handed polyproline type II helix conformation upon complex formation with the Fyn SH3 domain. Within this structure the arginine residue (Arg77) of Nef interacts with Asp 100 of the RT loop within the Fyn SH3 domain, and triggers a hydrogen-bond rearrangement which allows the loop to adapt to complement the Nef surface. The Arg96 residue of the Fyn SH3 domain is specifically accommodated in the same hydrophobic pocket of Nef. The Nef-Fyn complex forms in vivo and may have a crucial role in the T cell perturbating action of Nef by altering T cell receptor signaling.

Participants
Participant Of
Disease
Name Identifier Synonyms
Human immunodeficiency virus infectious disease 526 HIV infection
Authored
Reviewed
Created